Infantile agammaglobulinemia in man has been documented to be a disease due to the blockade of precursor B cell or pre-B cell differentiation to more mature B cells. The exact nature of this blockade is not known. Further analysis has been hampered by the lack of enriched cell population for precursor cells and pre-B cells. Using monoclonal antibodies specific for non B cells, an enrichment scheme is proposed and it will be tested. Concurrently, an immediate cloning system for EBV transformed precursor and pre-B cells will be developed to establish precursor B cell and pre-B cell lines from normals. Continued efforts will be made to derive cell lines from patients with infantile agammaglobulinemia with and without a clearly demonstrated X-linked inheritance mode. Cell lines will also be obtained from their parents. The availability of these cell lines as well as bone marrow populations enriched for precursor B cells will facilitate our search for monoclonal antibodies specific for these precursor cells. The state of Ig gene rearrangement in these precursor and pre-Beta cell lines will be probed. Their Ig synthetic patterns will be determined. Membrane antigenic differences between the precursor B and pre-B cell lines from normals and the patients with agammaglobulinemia will be sought. Preliminary studies will be done to determine if there are T cell factors important for the growth and differentiation of the precursor Beta and pre-Beta cells. The results of these studies will give new insight to the pathogenetic factors in the infantile agammaglobulinemia and will also provide clues for the mechanisms controlling early stages of normal B cell development.